1. Technical Field
This invention relates generally to the field of inducing the nucleation of selected crystal polymorphs from supersaturated solutions and specifically to a process of inducing the nucleation of selected crystal polymorphs from supersaturated solutions by using laser light to induce nucleation.
2. Prior Art
The crystal structure of a material determined by x-ray diffraction gives a complete picture of the arrangement of the atoms (or molecules) of the chemical species in the crystalline state. It is possible, however, for a given chemical species to have the ability to crystallize into more than one internally distinct structure. This ability is called polymorphism (or allotropism if the species is an element). Different polymorphs of the same material can display significant changes in their properties as well as in their structure.
The term “polymorphism” is contrasted with “morphology.” Crystals are solids with the atoms, molecules, or ions in a regular repeating structure. The overall external form is referred to as crystal morphology. The term morphology refers to the external shape of the crystal and the planes present, without reference to the internal structure. Crystals obtained experimentally can display different morphology based on different conditions, such as, for example, growth rate, stirring, and the presence of impurities. In contrast, as stated above, polymorphism refers to the internal alignment and orientation of the molecules. A substance can have several distinct polymorphs and only one morphology, or several distinct morphologies for only one polymorph. Just because the morphology changes does not mean there is a new polymorph, and vice versa. Unlike with different morphologies, one cannot tell by visual observation whether one has a different polymorph.
The prior art produces a substance with a known morphology and crystal structure. It does not produce a substance of unknown crystal structure (a new polymorph) or of unexpected structure (a known polymorph that would not normally occur under these conditions). As discussed above, there is an important distinction between morphology and polymorphism. Morphology is the external appearance of the crystal. In contrast, polymorphism refers to the internal structure of the crystal. It is important to note that crystals of a given substance with different morphologies have the same physical properties (such as melting point, solubility, electrical conductivity, etc) while different polymorphs of the same substance have different properties (e.g., diamond and graphite, which are different polymorphs of carbon).
Polymorphism is quite common in the elements and in inorganic and organic compounds and results in property changes. A dramatic example is carbon, which can crystallize as graphite or as diamond. Diamond is a cubic crystal, whereas graphite is hexagonal. In addition, properties such as hardness, density, shape, vapor pressure, dissolution rate, and electrical conductivity are all quite different for these two solids. These major differences in the properties of two polymorphs are not unique to carbon and can occur in all materials that display polymorphism. Many of the early identifications of polymorphs were minerals, such as calcium carbonate, which has three polymorphs (calcite, aragonite, and vaterite) and zinc sulfide, which has three polymorphs (wurtzite, sphalerite, and matraite). Some well known species have large numbers of polymorphs, for example water, which has eight different solid forms of ice. Organic molecular crystals often have multiple polymorphs that can be of great significance in the pharmaceutical, dye and explosives industries.
Under a given set of conditions, one polymorph is the thermodynamically stable form. This does not mean, however, that other polymorphs cannot exist or form at these conditions, only that one polymorph is stable and other polymorphs present can transform to the stable form. An example of this can be seen in heating (or cooling) a crystalline material with multiple polymorphs. As the temperature changes, the material will eventually enter a region where another polymorph is the stable form. The transformation of one polymorph to another, however, will occur at some rate that may be rapid or very slow. The transformation rate varies because the rate of transition of polymorphs depends on the type of structural changes that are involved.
Transformations can be categorized by the types of structural changes involved, which can roughly be related to the rate of transformation. For example, a transformation in which the lattice network is bent but not broken can be rapid. This type of transformation is known as displacive transformation of secondary coordination. Another type of rapid transformation can involve the breakage of weaker bonds in the crystal structure with the stronger bonds remaining in place. This is then followed by the rotation of parts of the molecule about the structure and the formation of new bonds. This type of transformation is a rotational disorder transformation. Slow transformations usually involve the breakage of the lattice network and major changes in the structure or type of bonding.
Polymorphic transformations can also be classified as first- or second-order transitions. In a first-order transition, the free energies of the two forms become equal at a definite transition temperature, and the physical properties of the crystal undergo significant changes upon transition. In a second-order transition, there is a relatively small change in the crystal lattice, and the two polymorphic forms will be similar. There is no abrupt transition point in a second order transition, although the heat capacity rises to a maximum at a second order transition point.
When a material is crystallized from solution, the transition between polymorphs can occur at a much higher rate because the transition is mediated by the solution phase. Polymorphs of a given material will have different solubilities at a given temperature, with the more stable material having a lower solubility (and a higher melting point) than the less stable polymorph. If two polymorphs are in a saturated solution, the less stable polymorph will dissolve and the more stable polymorph will grow until the transition is complete. The rate of the transition is a function of the difference in the solubility of the two forms and the overall degree of solubility of the compounds in solution. This transition requires that some amount of the stable polymorph be present, meaning that the stable polymorph must nucleate at least one crystal for the transition to begin. If a slurry of solution and crystals of a polymorph stable at a high temperature is cooled to a lower temperature, where another polymorph is the stable phase, the transition of the crystals already present will depend on the presence of nuclei of the new stable phase. The more of these nuclei present, the faster the transition will occur.
It is often possible to crystallize a metastable polymorph by applying a large supersaturation (for example rapid cooling) so that crystals of the metastable form appear before crystals of the stable form. When this occurs, if the solid is removed from the solution rapidly and dried, it is possible to obtain samples of a metastable polymorph that will not easily transform to the stable phase unless heated. If the crystals of the metastable polymorph are left in solution for any length of time, they will likely transform to the stable form by going through the solution phase. If seeds of the stable polymorph are added to the solution, the transition will occur more rapidly. At first-order phase-transition temperatures, the solubility of the two forms will be equal and both can exist.
When a material that displays polymorphism is crystallized, a metastable phase often appears first and then transforms into a stable form. This observation is summarized by Ostwald's step rule, which is also known as the Law of Successive Reactions. This law states that, in any process, the state that is initially obtained is not the most stable state but the least stable state that is closest, in terms of free-energy change, to the original state. In a crystallization process, therefore, it is possible to envision the phase transformation first occurring into the least stable polymorph (or even an amorphous phase), which transforms through a series of stages to successively more stable forms until the equilibrium form is obtained. While Ostwald's law has been observed in a wide variety of systems, it is most likely to be seen in organic molecular crystals.
Another interesting feature of organic molecular crystals is that the molecular conformation of a species can be different in two polymorphs of the same material. By molecular conformation, we are referring to the shape of the molecule. The same molecule can display different shapes (conformations by rotations about single bonds for example. Conformational polymorphism is the existence of polymorphs of the same substance in which the molecules present are in different conformations.
It is known that by subjecting some supersaturated solutions to laser light, the onset of nucleation occurs. Prior to nucleation, the supersaturated solution contains “clusters” of molecules that are not arranged in the lattice structure of a crystal. The laser light helps to align or organize the molecules in the clusters into a lattice arrangement resulting in the formation of nuclei and, after time, crystals. For a urea solution, it was shown that the laser could induce nucleation and the one and only known and expected polymorph for urea was obtained. Garetz, B. A. et al., Nonphotochemical, Polarization-Dependent, Laser-Induced Nucleation in Supersaturated Aqueous Urea Solutions, Physical Review Letters, Vol. 77, No. 16, pp. 3475-6 (1996).
The Garetz article does not disclose the creation of different, unexpected polymorphs or that different, unexpected polymorphs could be created using laser induced nucleation, as disclosed and claimed in the present patent application. More specifically, the Garetz adicle discloses the effect laser-induced nucleation has on the orientation of the molecules. Specifically, the Garetz article discloses that the polarization dependence of the crystallite orientation is consistent with a mechanism in which the electric field of the light plays a major role and that urea molecules are being aligned by the applied optical field, just as they are in the optical Kerr effect, also known as light-induced birefringence. The Garetz article further discloses that only urea's anisotropic polarizability is responsible for electrio-field-induced alignment at optical frequencies, thus, according to the Garetz mechanism, urea molecules in a cluster will tend to align with their C2 axes parallel to an applied electric field, E, growing into a crystallite with the needle axis parallel to E.
The discovery published in the Garetz article is a photophysical phenomenon in which the laser induced crystallization of urea causes the alignment of the urea molecules by the applied optical field. The crystals that result from the experimentation disclosed in the Garetz article were known and expected crystals. The novelty of the Garetz article is that the laser light causes the urea molecules to align, facilitating the nucleation into the known crystals. This is substantially different from the invention disclosed and claimed in the present patent application, which is the creation of different polymorphs not normally obtained using current art nucleation methods.
An application of the Garetz et al principles is in U.S. Pat. No. 5,976,325 to Blanks that discloses a method for producing a substance with a known morphology and crystal structure in aluminate solution. Blanks '325 discloses a self-seeding processes to obtain the most stable crystal structure of sodium aluminate from a supersaturated aluminate solution (i.e. Bayer Process solution) and does not implicate the polymorphism of the substance. More distinctively, the process in Blanks '325 is primarily for destroying impurities in the solution, and the light used is absorbed by the materials. Blanks '325 discloses a process for forming a precipitated alumina hydrate, comprising the steps of providing a sodium aluminate solution; and illuminating said sodium aluminate solution with light wave energy produced by the near infrared wavelength, linearly polarized output of a laser to form a precipitated alumina hydrate where no external seed is added. Much like the Garetz article, Blanks '325 discloses a method for obtaining a known crystal in a process for forming a precipitated alumina hydrate such as aluminum trihydroxide by providing a supersaturated sodium aluminate solution and treating the solution by illumination with pulsed near infrared light wave energy, spatially and temporally overlapped inside the solution, so as to produce a photo-induced nucleation of purified gibbsite crystals, without the need for external seed.
More specifically, Blanks '325 discloses a laser induced precipitation process for forming known alumina hydrate products. It does not disclose or claim, or even discuss, the formation of different polymorphs. It merely discloses a method for obtaining a known alumina hydrate for use in a conventional alumina purification process. As discussed above, a polymorph generally is defined as any of the crystalline forms of a substance capable of having different crystalline structures. Blanks '325 does not disclose whether a specific polymorph of alumina hydrate is desired and, more importantly, whether a different polymorph of alumina hydrate that is not typically created for use in the purification process (or an unknown polymorph of alumina hydrate) is created.
Blanks '325 merely discloses precipitating alumina hydrate for purification employing a laser treatment process properly to introduce infrared light into green Bayer liquor, e.g., such as by way of example from the first source facility, to provide enhancements in alumina yield of as much as 50 grams/liter without the addition of seed. While gibbsite may be the preferred form of alumina hydrate (whether for purification or for economic reasons) mentioned in Blanks '325, this apparently is a preferred form throughout the industry. Gibbsite Al(OH)3 is a valuable and desirable mineral found in bauxite. This, coupled with the lack of disclosure on how to prepare different polymorphs, and polymorphs that normally would not result under the same conditions without the use of the selected light, indicates that Blanks '325 does not contemplate the present invention.
The mechanism by which the Blanks '325 method works also is different than that of the present patent application. Blanks '325 discloses that the laser removes undesirable organic compounds that are generally considered as inhibitors to alumina hydrate precipitation. In other words, the laser works by photochemically destroying organic impurities, thus permanently changing the conditions (i.e., with inhibitors removed) under which the nucleation proceeds. The method therefore requires that the laser light be absorbed by organic impurities in the solution, so that in Blanks '325 the wavelength of the laser needs to be tuned to match the absorption bands of the organic impurities in their samples. One feature of Blanks '325 is that by absorbing near infrared light, they are able to induce the photochemistry needed to destroy their organic impurities. In contrast, the present invention preferably involves no light absorption by the sample.
The Blanks '325 preferred embodiment employs any laser, which may be mode-locked so to emit sub-nanosecond pulses of near infrared light at an energy level of about 500-700 milliwatts. Typical cw mode-locked lasers have repetition rates of about 100 MHz (100 million pulses/second). For the Blanks '325 preferred laser, this corresponds to an energy/pulse of about 5-7 nanojoules. This is a very different type of laser than a Q-switched laser with nanosecond pulses with energy/pulse of about 0.1 Joules. The Blanks '325 pulses have an energy per pulse about ten million times weaker than the Q-switched laser used in the example of the present invention, and the electric fields associated with Blanks '325 laser pulses several orders of magnitude weaker than the electric fields associated with the lasers used in the present invention. Using a laser like the one disclosed in Blanks '325 would not induce nucleation in the glycine of the present invention.